The overall goal of this research proposal is to determine the interrelationship between endocrine, vascular and neural brain aging. Studies assess age-related changes in the brain and vasculature, address whether chronic, pulsatile growth hormone releasing factor (GRF) administration, resulting in growth hormone and insulin-like growth factor 1 (IGF-1) increases, will delay or prevent age-related changes in the brain, and assess the relationship between growth hormone receptors and the expression of IGF-1. The studies will assess age-related changes in the central auditory system, specifically the superior olivary complex and the auditory cortex, as well as sensory/motor cortex. The superior olivary complex is a hindbrain auditory center involved in binaural analysis and which shows age-related changes. Many age-related decreases in auditory function can be related in a simple manner to changes in the ear. However, there are indications that central processing may be impaired as well. This is of clinical significance as the same processing involved in sound localization also has an important role in speech discrimination. The working hypothesis is that age-related decreases in growth hormone and plasma IGF-1 will lead to a decrease in cerebral vascular production of IGF-1 with resulting morphological and functional changes in the brain. In order to address the complex relationship between endocrine, vascular, and neural brain aging, three specific aims have been developed: 1) Assessing age-related neural and vascular changes in the brain, specifically central auditory and sensory/motor structures; we will study neuron, glial, and capillary density and size; synaptic density and length; and neurotransmitter distribution. 2) Determining whether increases in plasma growth hormone by chronic/pulsatile GRF administration ameliorates age-related changes documented in the experiments outlined in Specific Aim 1. 3) Determining whether the vasculature is the site of action of growth hormone endocrine actions and subsequently the source of local IGF-1 expression and whether there are age-related changes in IGF-1 mRNA, IGF-1 receptors, or growth hormone receptors. Analyzing the dynamics of GH receptors, IGF-1 mRNA, and IGF-1 receptor mRNA distribution in response to aging and GRF administration will provide data to understand the mechanisms involved in the endocrine, vascular, and neural confluence of aging. These studies should provide valuable information on brain aging; the relationship between IGF-1 and neural and vascular changes; and address potential mechanisms of aging. The results will be useful in designing therapeutic protocols for age-related pathologies such as vascular dementia.